ZhenMin Mao

Name: 毛振民; ZhenMin Mao

Organization: Shanghai Jiaotong University

Department:

Title:

Chemicals
References

Design, synthesis and biological evaluation of N-alkyl or aryl substituted isoindigo derivatives as potential dual cyclin-dependent kinase 2 (CDK2)/glycogen synthase kinase 3β (GSK-3β) phosphorylation inhibitors

Co-reporter:Ping Zhao, Yanzhong Li, Guangwei Gao, Shuai Wang, Yun Yan, Xiaoping Zhan, Zenglu Liu, Zhenmin Mao, Shaoxiong Chen, Liqun Wang

European Journal of Medicinal Chemistry 2014 Volume 86() pp:165-174

Publication Date(Web):30 October 2014

DOI:10.1016/j.ejmech.2014.08.049

•New isoindigo derivatives as dual CDK2/GSK-3β inhibitor were synthesized.•Anti-proliferative activity was tested by SRB assay and preliminary SAR was given.•Compound 6k blocked the cell cycle at S phase and induced the apoptosis of cells.•6k affected the level of CDK2, cyclin A and Wnt/β-catenin pathway proteins.•Docking studies explained the binding mode of 6k with GSK-3β.A series of N-alkyl or aryl substituted isoindigo derivatives have been synthesized and their anti-proliferative activity was evaluated by Sulforhodamine B (SRB) assay. Some of the target compounds exhibited significant antitumor activity, including compounds 6h and 6k (against K562 cells), 6i (against HeLa cells) and 6j (against A549 cells). N-(p-methoxy-phenyl)-isoindigo (6k) exhibited a high and selective anti-proliferative activity against K562 cells (IC50 7.8 μM) and induced the apoptosis of K562 cells in a dose-dependent manner. Compound 6k arrested the cell cycle at S phase in K562 cells by decreasing the expression of cyclin A and CDK2, which played critical roles in DNA replication and passage through G2 phase. Moreover, compound 6k down-regulated the expression of p-GSK-3β (Ser9), β-catenin and c-myc proteins, up-regulated the expression of GSK-3β, consequently, suppressed Wnt/β-catenin signaling pathway and induced the apoptosis of K562 cells. The binding mode of compound 6k with GSK-3β was simulated using molecular docking tools. All of these studies gave a better understanding to the molecular mechanisms of this class of agents and clues to develop dual CDK2/GSK-3β (Ser9) phosphorylation inhibitors applied in cancer chemotherapy.

A Novel Facile Synthesis Method of N-Vinylpyrroles

Co-reporter:Tian Lan;Xiaofen Chen;Zenglu Liu

Journal of Heterocyclic Chemistry 2013 Volume 50( Issue 5) pp:1094-1098

Publication Date(Web):

DOI:10.1002/jhet.1102

A facile and effective synthesis of N-vinylpyrroles had been explored. The synthetic approach was practicable for preparation of N-vinylpyrroles for the mild reaction conditions and readily available materials, compared with previously inaccessible N-vinylpyrroles with electron-withdrawing groups, especially these pyrroles bearing alkaline sensitive substitution groups.

Two new types of copolymer membranes controlling clonidine zero-order release

Co-reporter:Xiaoping Zhan;Guochun Tang;Sijing Chen

Journal of Applied Polymer Science 2007 Volume 106(Issue 5) pp:3016-3022

Publication Date(Web):9 AUG 2007

DOI:10.1002/app.26954

Two new types of membranes were synthesized by UV curing in our laboratory. The first type of membrane was made of three monomers: 2-hydroxy-3-phenoxypropylacrylate(A), 4-hydroxybutyl acrylate(B), and 2-methyl-2-nitropropyl methacrylate(C1). The second type of membrane was made of the same monomers A and B, and 2-butoxyethyl methacrylate(C2). Permeation properties of clonidine releasing through two new types of copolymer membranes were studied. The effects of the ratios of monomers, the thicknesses of membranes, and the concentration of clonidine on the permeation rates were studied. It was found that both copolymer membranes could control clonidine zero-order release. The permeation rates of the first optimized membrane were linearly dependent on the square root of the drug concentration. The permeation rates of the second optimized membrane had no significant difference when the concentration of clonidine varied in the range of 3.0–5.0 mg mL⁻¹. Furthermore, both optimized membranes were characterized by FTIR, DSC, and SEM. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007

A new copolymer membrane cured by 2-hydroxy-3-phenoxypropylacrylate, 4-hydroxybutyl acrylate, and isobutyl methacrylate controlled clonidine linear release in the transdermal drug delivery system

Co-reporter:Xiaoping Zhan;Sijing Chen;Guochun Tang

Polymers for Advanced Technologies 2007 Volume 18(Issue 5) pp:392-396

Publication Date(Web):26 FEB 2007

DOI:10.1002/pat.901

The main objective of this present study was to synthesize a new type of copolymer membrane that presented a linear release property in clonidine transdermal drug delivery system. Three monomers, 2-hydroxy-3-phenoxypropylacrylate, 4-hydroxybutyl acrylate, and isobutyl methacrylate were treated under strong power UV radiation to prepare a new type of copolymer membrane. The effects of monomers' ratios, membrane thickness, and clonidine concentration on the permeation rates were investigated. It was discovered that the membrane controlled clonidine near zero-order release. Furthermore, the membrane was characterized by FTIR, DSC, and SEM. Copyright © 2007 John Wiley & Sons, Ltd.